RESUMO
Objective: Perioperative deep prosthetic joint infection (PJI) is a serious postoperative complication of total hip arthroplasty (THA). We aimed to compare the efficacy of cefazolin administered within 24 and 48 h of primary THA for PJI prophylaxis. Methods: In this retrospective study, 720 patients were divided into two groups depending on whether cefazolin was administered as a single injection of 2 g twice daily within 24 (24-h group) or 48 h of surgery and the following day (48-h group). Sex, age at surgery, body mass index, co-existing diseases, blood test data, and PJI risk factors were evaluated. Results: The 24- and 48-h groups included 364 and 356 patients, respectively. Diabetes mellitus was the most common risk factor for PJI in both groups. The corresponding incidence of perioperative deep PJI following primary THA was 0.55% and 0.28% in the 24- and 48-h groups, respectively. There was no significant difference in patient background characteristics between the groups. Conclusions: Cefazolin administration within 24 h of primary THA may be appropriate for perioperative deep PJI. Level of Evidence II; Retrospective study .
Objetivo: A infecção de prótese articular (IPA) perioperatória profunda é uma grave complicação pós-operatória da artroplastia total de quadril (ATQ). Este estudo buscou comparar a eficácia da cefazolina administrada dentro de 24 e 48 horas após ATQ para profilaxia de IPA. Métodos: Neste estudo retrospectivo, 720 pacientes foram divididos em dois grupos, que receberam cefazolina em uma injeção de 2g duas vezes por dia nas primeiras 24 e 48 horas (grupos de 24 e 48 horas), respectivamente. Foram avaliados sexo, idade na data da cirurgia, índice de massa corporal, comorbidades, testes sanguíneos e fatores de risco para IPA. Resultados: Os grupos de 24 e 48 horas incluíram, respectivamente, 364 e 356 pacientes. O fator de risco para IPA mais comum nos dois grupos foi o diabetes mellitus. A incidência de IPA perioperatória profunda após ATQ foi, respectivamente, de 0,55% e 0,28% nos grupos de 24 e 48 horas. Não houve diferença significativa nas características gerais dos pacientes entre os dois grupos. Conclusão: A administração de cefazolina dentro de 24 horas após ATQ primária pode ser adequada para IPA perioperatória profunda. Nível de Evidência II; Estudo retrospectivo .
RESUMO
Infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) are still associated with significant morbidity and mortality. Treatment failures of cefazolin (CFZ) have been reported and probably related to the inoculum effect. New treatments for severe MSSA infections are needed and ceftaroline fosamil (CPT) could be an option. Our aim was to describe the clinical characteristics of five patients with complicated MSSA bacteremia failing CFZ and successfully treated with CPT. We performed a retrospective chart review in a Hospital in Buenos Aires, Argentina; in a 12-month period, five patients (24%) of 21 with MSSA bacteremia experienced CFZ failure and were salvaged with CPT. The median time of CFZ therapy was 10 days before changing to CPT; four patients had evidence of metastatic spread and 2 had endocarditis. All patients experienced microbiological and clinical cure with CPT, which was used as monotherapy in 4 and in combination with daptomycin in another. One patient discontinued CPT due to neutropenia on day 23 of treatment. In patients with MSSA BSI failing current therapy, CPT could be a good therapeutic option.
Las infecciones causadas por Staphylococcus aureus sensible a la meticilina (SASM) todavía se asocian con una morbilidad y mortalidad significativas. Se han informado fallas en el tratamiento de cefazolina (CFZ) probablemente relacionadas con efecto inóculo. Nuevos tratamientos son necesarios para estas infecciones y ceftarolina fosamil (CPT) podría ser una opción. Nuestro objetivo fue describir las características clínicas de cinco pacientes con bacteriemia por SASM complicada con falla a CFZ y que fueron exitosamente tratados con CPT. Realizamos una revisión retrospectiva de historias clínicas en un hospital de Buenos Aires, Argentina; en un período de 12 meses, cinco pacientes (24%) de 21 con bacteriemia por SASM experimentaron falla a CFZ y fueron tratados con CPT. La mediana de tiempo de la terapia con CFZ fue de 10 días antes de cambiar a CPT; cuatro pacientes presentaban evidencia de diseminación metastásica y 2 tenían endocarditis. Todos los pacientes experimentaron curación microbiológica y clínica con CPT, que se utilizó como monoterapia en 4 y en combinación con daptomicina en otro. Un paciente interrumpió CPT debido a neutropenia el día 23 de tratamiento. En enfermos con infecciones graves por SASM que fallan en la terapia actual, CPT podría ser una buena opción terapéutica.
Assuntos
Bacteriemia , Daptomicina , Infecções Estafilocócicas , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cefazolina/uso terapêutico , Cefalosporinas , Daptomicina/uso terapêutico , Humanos , Meticilina/uso terapêutico , Estudos Retrospectivos , Terapia de Salvação , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , CeftarolinaRESUMO
Abstract Infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) are still associated with significant morbidity and mortality. Treatment failures of cefazolin (CFZ) have been reported and probably related to the inoculum effect. New treatments for severe MSSA infections are needed and ceftaroline fosamil (CPT) could be an option. Our aim was to describe the clinical characteristics of five patients with com plicated MSSA bacteremia failing CFZ and successfully treated with CPT. We performed a retrospective chart review in a Hospital in Buenos Aires, Argentina; in a 12-month period, five patients (24%) of 21 with MSSA bacteremia experienced CFZ failure and were salvaged with CPT. The median time of CFZ therapy was 10 days before changing to CPT; four patients had evidence of metastatic spread and 2 had endocarditis. All patients experienced microbiological and clinical cure with CPT, which was used as monotherapy in 4 and in combination with daptomycin in another. One patient discontinued CPT due to neutropenia on day 23 of treatment. In patients with MSSA BSI failing current therapy, CPT could be a good therapeutic option.
Resumen Las infecciones causadas por Staphylococcus aureus sensible a la meticilina (SASM) todavía se asocian con una morbilidad y mortalidad significativas. Se han informado fallas en el tratamiento de cefazolina (CFZ) probablemente relacionadas con efecto inóculo. Nuevos tratamientos son necesarios para estas infecciones y ceftarolina fosamil (CPT) podría ser una opción. Nuestro objetivo fue describir las características clínicas de cinco pacientes con bacteriemia por SASM complicada con falla a CFZ y que fueron exitosamente tratados con CPT. Realizamos una revisión retrospectiva de historias clínicas en un hospital de Buenos Aires, Argentina; en un período de 12 meses, cinco pacientes (24%) de 21 con bacteriemia por SASM experimentaron falla a CFZ y fueron tratados con CPT. La mediana de tiempo de la terapia con CFZ fue de 10 días antes de cambiar a CPT; cuatro pacientes presentaban evidencia de diseminación metastásica y 2 tenían endocarditis. Todos los pacientes experimen taron curación microbiológica y clínica con CPT, que se utilizó como monoterapia en 4 y en combinación con daptomicina en otro. Un paciente interrumpió CPT debido a neutropenia el día 23 de tratamiento. En enfermos con infecciones graves por SASM que fallan en la terapia actual, CPT podría ser una buena opción terapéutica.
RESUMO
Cefazolin (CFZ) is a ubiquitous antibiotic in hospital settings and has been recognized as an emerging contaminant due to its ecotoxicity. Despite the growing concern around this compound, the literature addressing feasible advanced techniques for CFZ uptake from aqueous matrices is still scarce. Thus, the objective of this work was to evaluate the adsorption of cefazolin on Spectrogel® organoclay in a batch system as an efficient remediation method. The optimization of experimental conditions was determined by a central composite rotational design. A pH study, as well as equilibrium, kinetic, and thermodynamic assays, was performed to assess the adsorption of CFZ on Spectrogel®. The kinetic and equilibrium models that best described the system were the external mass transfer resistance and Sips models, respectively. A removal efficiency above 80% was achieved, and the maximum adsorption capacity at 25 °C was 398.6 mg g-1. The post-process contaminated organoclay was thermally regenerated. The outcomes of this work indicate that Spectrogel® is an environmentally friendly adsorbent for the removal of cefazolin from wastewater.
Assuntos
Águas Residuárias , Poluentes Químicos da Água , Adsorção , Antibacterianos , Cefazolina , Concentração de Íons de Hidrogênio , Cinética , Projetos de Pesquisa , Termodinâmica , Águas Residuárias/química , Poluentes Químicos da Água/análiseRESUMO
Cefazolin (CFZ) is an antibiotic widely used in veterinary and human medicine that has been detected in high residual levels in the environment and is therefore considered an emerging contaminant. This work evaluated the adsorption of this contaminant by Spectrogel® type C organoclay, in continuous mode using a fixed-bed column. The fluid dynamics and the effect of the CFZ concentration were evaluated. In addition, prior and post-process organoclay were characterized. The continuous system under the conditions of C0 = 0.3 mmol/L and Q = 0.1 mL/min presented lower values of mass transfer zone (5.88 cm), whereas the system with C0 = 0.5 mmol/L and Q = 0.1 mL/min achieved higher CFZ adsorption capacity (20 µmol/g). Phenomenological and mass-transfer models were applied to the experimental data. The dual-site diffusion (DualSD) model better described the breakthrough (BTC) data. Furthermore, density functional theory (DFT) calculation was performed at the molecular level to provide a better comprehension of CFZ adsorption.
Assuntos
Poluentes Químicos da Água , Purificação da Água , Adsorção , Antibacterianos , Cefazolina , Humanos , Modelos Teóricos , Poluentes Químicos da Água/análiseRESUMO
ABSTRACT Objective Perioperative deep prosthetic joint infection (PJI) is a serious postoperative complication of total hip arthroplasty (THA). We aimed to compare the efficacy of cefazolin administered within 24 and 48 h of primary THA for PJI prophylaxis. Methods In this retrospective study, 720 patients were divided into two groups depending on whether cefazolin was administered as a single injection of 2 g twice daily within 24 (24-h group) or 48 h of surgery and the following day (48-h group). Sex, age at surgery, body mass index, co-existing diseases, blood test data, and PJI risk factors were evaluated. Results The 24- and 48-h groups included 364 and 356 patients, respectively. Diabetes mellitus was the most common risk factor for PJI in both groups. The corresponding incidence of perioperative deep PJI following primary THA was 0.55% and 0.28% in the 24- and 48-h groups, respectively. There was no significant difference in patient background characteristics between the groups. Conclusions Cefazolin administration within 24 h of primary THA may be appropriate for perioperative deep PJI. Level of Evidence II; Retrospective study.
RESUMO Objetivo A infecção de prótese articular (IPA) perioperatória profunda é uma grave complicação pós-operatória da artroplastia total de quadril (ATQ). Este estudo buscou comparar a eficácia da cefazolina administrada dentro de 24 e 48 horas após ATQ para profilaxia de IPA. Métodos Neste estudo retrospectivo, 720 pacientes foram divididos em dois grupos, que receberam cefazolina em uma injeção de 2g duas vezes por dia nas primeiras 24 e 48 horas (grupos de 24 e 48 horas), respectivamente. Foram avaliados sexo, idade na data da cirurgia, índice de massa corporal, comorbidades, testes sanguíneos e fatores de risco para IPA. Resultados Os grupos de 24 e 48 horas incluíram, respectivamente, 364 e 356 pacientes. O fator de risco para IPA mais comum nos dois grupos foi o diabetes mellitus. A incidência de IPA perioperatória profunda após ATQ foi, respectivamente, de 0,55% e 0,28% nos grupos de 24 e 48 horas. Não houve diferença significativa nas características gerais dos pacientes entre os dois grupos. Conclusão A administração de cefazolina dentro de 24 horas após ATQ primária pode ser adequada para IPA perioperatória profunda. Nível de Evidência II; Estudo retrospectivo.
RESUMO
The cefazolin inoculum effect (CzIE) has been associated with therapeutic failures and mortality in invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections. A diagnostic test to detect the CzIE is not currently available. We developed a rapid (â¼3 h) CzIE colorimetric test to detect staphylococcal-ß-lactamase (BlaZ) activity in supernatants after ampicillin induction. The test was validated using 689 bloodstream MSSA isolates recovered from Latin America and the United States. The cefazolin MIC determination at a high inoculum (107 CFU/ml) was used as a reference standard (cutoff ≥16 µg/ml). All isolates underwent genome sequencing. A total of 257 (37.3%) of MSSA isolates exhibited the CzIE by the reference standard method. The overall sensitivity and specificity of the colorimetric test was 82.5% and 88.9%, respectively. Sensitivity in MSSA isolates harboring type A BlaZ (the most efficient enzyme against cefazolin) was 92.7% with a specificity of 87.8%. The performance of the test was lower against type B and C enzymes (sensitivities of 53.3% and 72.3%, respectively). When the reference value was set to ≥32 µg/ml, the sensitivity for isolates carrying type A enzymes was 98.2%. Specificity was 100% for MSSA lacking blaZ The overall negative predictive value ranged from 81.4% to 95.6% in Latin American countries using published prevalence rates of the CzIE. MSSA isolates from the United States were genetically diverse, with no distinguishing genomic differences from Latin American MSSA, distributed among 18 sequence types. A novel test can readily identify most MSSA isolates exhibiting the CzIE, particularly those carrying type A BlaZ. In contrast to the MIC determination using high inoculum, the rapid test is inexpensive, feasible, and easy to perform. After minor validation steps, it could be incorporated into the routine clinical laboratory workflow.
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Cefazolina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefazolina/farmacologia , Testes Diagnósticos de Rotina , Humanos , América Latina , Meticilina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/genéticaRESUMO
INTRODUCTION: GBS colonization is an important risk factor for maternal and neonatal infection morbidity and mortality. Intrapartum antibiotics may prevent vertical transmission of GBS from colonized mothers to their babies. The objective of this study was to evaluate the effectiveness of cefazolin prophylactic regimen for GBS disease, comparing it to the established penicillin-based protocols, given the opportunity provided by the temporary unavailability of first-choice antibiotics in Brazil. METHODOLOGY: A retrospective analysis was conducted at the Hospital Femina Obstetrics Service between January and December 2015. Ninety-eight pregnant women received standard penicillin (70 patients) or ampicillin (28 patients) antibiotic prophylaxis, and 251 pregnant women received an alternative prophylaxis with cefazolin during the study period. Risk factor, Maternal and neonatal outcomes were evaluated and compared between groups. RESULTS: No significant difference was found in maternal (RR = 0.71; IC 95%:0.30-1.68; p = 0.709) and neonatal (RR = 0.84; IC 95%:0.61-1.15; p = 0.271) outcomes between those patients using the alternative antibiotic prophylaxis in comparison to the standard antibiotics, with the dependent variable of maternal and neonatal outcomes grouped and controlled for potential confounding variables. CONCLUSIONS: The antibiotics used as alternatives to penicillin and ampicillin for the prevention of maternal-fetal GBS disease are poorly studied, and this study indicate that cefazolin can be an optimal choice, offering safety in the use of this antibiotic in situations where penicillins are contraindicated or unavailable.
Assuntos
Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/prevenção & controle , Streptococcus agalactiae/efeitos dos fármacos , Adolescente , Adulto , Brasil , Cefazolina/uso terapêutico , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Streptococcus agalactiae/fisiologia , Adulto JovemRESUMO
Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal ß-lactamases. Four variants of staphylococcal ß-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal ß-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the ß-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for ß-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant ß-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal ß-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.
Assuntos
Antibacterianos/farmacologia , Cefazolina/farmacologia , Farmacorresistência Bacteriana/genética , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , beta-Lactamases/classificação , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Humanos , América Latina/epidemiologia , Testes de Sensibilidade Microbiana , Epidemiologia Molecular , Filogenia , Prevalência , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/enzimologia , Sequenciamento Completo do Genoma , beta-Lactamases/genéticaRESUMO
BACKGROUND: Methicillin-susceptible Staphylococcus aureus (MSSA) is a frequent cause of bloodstream infections (BSI). Treatment with nafcillin (NAF) has been preferred to cefazolin (CFZ). However, comparable outcomes have been found with CFZ with possibly lower risk for side-effects. This study compared safety and effectiveness of NAF versus CFZ for MSSA BSI. METHODS: This single center retrospective study evaluated adults admitted with MSSA BSI who received NAF or CFZ. Patients receiving ≥24 h of antibiotics were included for safety analyses. Patients receiving NAF or CFZ for ≥75% of a 14 day minimum treatment course were assessed for clinical effectiveness. The primary safety outcome was incidence of renal toxicity with multiple secondary safety endpoints. Clinical success was defined as symptom resolution, repeat negative cultures, lack of additional therapy for presumed failure, and lack of recurrence within 30 days. RESULTS: A total of 130 patients receiving NAF (n = 79) or CFZ (n = 51) were included for safety analysis. Of those, 90 met criteria for effectiveness assessment (NAF n = 40, CFZ n = 50). Baseline characteristics were well matched. NAF was associated with a higher incidence of nephrotoxicity compared to CFZ (25% vs. 2%, RR 1.31, 95% CI 1.15-1.5, p < 0.001), allergic reactions (p = 0.01) and a trend for hepatotoxicity (p = 0.08). Clinical success was achieved in 82% NAF and 94% CFZ treated patients (p = 0.1). CONCLUSION: CFZ was associated with less nephrotoxicity and no difference in clinical success compared to NAF for MSSA BSI. A prospective study comparing NAF to CFZ for MSSA BSI should be conducted to elucidate differences in therapies.